Background & Aim: Suppressor of cytokine signaling 1 (SOCS1) is considered a tumor suppressor due to frequent epigenetic and micro-RNA-mediated downregulation in many cancers including prostate cancer (PCa). Increased risk of disease recurrence in PCa is associated with elevated expression of miR-30d that targets SOCS1 mRNA. The tumor suppressor function of SOCS1 is mediated via diverse mechanisms such as inhibition of JAK-STAT signaling pathway, co-operation with p53, inhibition of MET receptor tyrosine kinase signaling and attenuation of the paradoxical oncogenic potential of CDKN1A (p21CIP1; p21). The goal of this study is to determine the expression of SOCS1 and its downstream targets (p53, MET and p21) in human PCa specimens in order to assess their significance as prognostic biomarkers.
Methodology: We have constructed tissue microarrays (TMA) from 78 archived prostatectomy specimens. International Society of Urological Pathology (ISUP) guidelines based on the Gleason patterns were used to group the specimens. The common prostate cancer-related markers Ki67, prostein and androgen receptor, as well as SOCS1, p53, MET and p21 protein expression were evaluated in the TMAs by immunohistochemical staining. We evaluated the association between the staining intensities of these markers and ISUP grade groups, local invasion or lymph node metastasis using appropriate statistical methods.
Results: The prostatic epithelium showed diffuse SOCS1 staining that was similar to but distinct from that of prostein. An inverse correlation was observed between SOCS1 protein expression and the ISUP grade (ρ =-0.4687, p <0.0001). SOCS1 staining also correlated positively with prostein (ρ=0.3511, p=0.0016) and negatively with Ki67 (ρ=-0.2444, p=0.031). However, the correlations between SOCS1 staining and those of p53, MET or p21 were not statistically significant. Nonetheless, p21 staining displayed significant positive correlation with androgen receptor expression (ρ=-0.1388, p=0.0003). A subset of PCa specimens from patients with regional lymph node metastasis showed reduced SOCS1 expression and increased expression of MET and p21.
Conclusions: SOCS1 and p21 protein expression in prostatectomy specimens may have a prognostic value in identifying the aggressive disease. Further testing of this prediction requires prospective studies on larger cohorts of PCa patients with metastatic disease.